EP2537528B1 - Pharmaceutical compositions containing beta- and alpha-galactosidase and their use in the treatment of gastroesophageal reflux disease - Google Patents
Pharmaceutical compositions containing beta- and alpha-galactosidase and their use in the treatment of gastroesophageal reflux disease Download PDFInfo
- Publication number
- EP2537528B1 EP2537528B1 EP12172907.3A EP12172907A EP2537528B1 EP 2537528 B1 EP2537528 B1 EP 2537528B1 EP 12172907 A EP12172907 A EP 12172907A EP 2537528 B1 EP2537528 B1 EP 2537528B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- galactosidase
- treatment
- reflux disease
- gastroesophageal reflux
- compositions containing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 208000021302 gastroesophageal reflux disease Diseases 0.000 title claims description 20
- 102000005840 alpha-Galactosidase Human genes 0.000 title claims description 15
- 108010030291 alpha-Galactosidase Proteins 0.000 title claims description 15
- 102000005936 beta-Galactosidase Human genes 0.000 title claims description 12
- 108010005774 beta-Galactosidase Proteins 0.000 title claims description 12
- 238000011282 treatment Methods 0.000 title claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 239000000203 mixture Substances 0.000 claims description 21
- 235000016709 nutrition Nutrition 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000010992 reflux Methods 0.000 description 13
- 208000024891 symptom Diseases 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 210000005070 sphincter Anatomy 0.000 description 4
- 230000037213 diet Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229940126409 proton pump inhibitor Drugs 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical class OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010030216 Oesophagitis Diseases 0.000 description 2
- 206010067171 Regurgitation Diseases 0.000 description 2
- 235000006886 Zingiber officinale Nutrition 0.000 description 2
- 229960004998 acesulfame potassium Drugs 0.000 description 2
- 235000010358 acesulfame potassium Nutrition 0.000 description 2
- 239000000619 acesulfame-K Substances 0.000 description 2
- 230000009858 acid secretion Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 210000003736 gastrointestinal content Anatomy 0.000 description 2
- 235000008397 ginger Nutrition 0.000 description 2
- 208000024798 heartburn Diseases 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 239000000612 proton pump inhibitor Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 208000023514 Barrett esophagus Diseases 0.000 description 1
- 208000023665 Barrett oesophagus Diseases 0.000 description 1
- 241000234314 Zingiber Species 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000024330 bloating Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- -1 elixirs Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 239000001841 zingiber officinale Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2465—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1) acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase (3.2.1.22)
Definitions
- the present invention relates to pharmaceutical or nutritional compositions containing ⁇ -galactosidase and ⁇ -galactosidase. Said compositions are useful in the prevention and/or treatment of gastroesophageal reflux disease.
- GORD gastro-oesophageal reflux disease
- Reflux of the stomach contents into the oesophagus is a physiological phenomenon; when the frequency of the episodes increases, the reflux becomes harmful to the oesophageal mucosa and causes the appearance of symptoms and complications, such as oesophagitis and Barrett's oesophagus.
- the treatment is based on suppression of the acid secretion.
- PPIs therefore represent the first-choice treatment in GERD.
- H2 antihistamines (anti-H2s) and antacids are also used to treat the symptoms of gastroesophageal reflux disease.
- lactose increases acid reflux episodes and markedly influences the function of the lower oesophageal sphincter.
- the effects of lactose are mediated by the production of short-chain fatty acids, which derive from the metabolism of lactose by the bacterial flora of the colon ( Piche et al., 2000; Am J Physiol Gastrointest Liver Physiol 278: G578-84 ).
- fructo-oligosaccharides also induces effects on the pressure of the lower oesophageal sphincter and the pH of the oesophageal lumen similar to those observed with lactose administration ( Piche et al., Gastroenterology 2003; 124: 894-902 ).
- the present invention relates to pharmaceutical or nutritional compositions containing ⁇ -galactosidase and ⁇ -galactosidase.
- the invention also relates to the use of said compositions in the prevention and/or treatment of gastroesophageal reflux disease.
- the present invention relates to pharmaceutical or nutritional compositions containing ⁇ -galactosidase and ⁇ -galactosidase as active ingredients.
- compositions containing ⁇ -galactosidase and ⁇ -galactosidase are useful in the prevention and/or treatment of gastroesophageal reflux disease (GERD).
- Said compositions have a different action mechanism from those of the medicaments currently used (acid secretion inhibitors) in that they inhibit reflux or at least reduce its frequency.
- the present invention represents a new therapeutic strategy, which is designed in particular for non-responders and patients with a poor response to the current treatments based on proton pump inhibitors.
- compositions to which the present invention relates can be also added to the existing treatments (as an "add-on therapy"), leading to a significant improvement in the quality of life of many patients with gastroesophageal reflux disease.
- the present invention relates to pharmaceutical or nutritional compositions containing a combination of the active ingredients, mixed with at least one pharmaceutically acceptable excipient or carrier.
- compositions are preferably administered orally.
- compositions for the prevention and/or treatment of gastroesophageal reflux disease containing ⁇ -galactosidase and ⁇ -galactosidase as active ingredients can be formulated by conventional methods.
- the preferable dosage forms are solid formulations for oral administration, such as powders, granules, tablets, pills and capsules.
- the active ingredients can be mixed with at least one pharmaceutically acceptable excipient or carrier, such as an inert diluent, a lubricant such as magnesium stearate, an anti-caking agent such silicon dioxide, a preservative, an antioxidant, a disintegrant, a binder, a thickening agent, a buffer, a sweetener such as acesulfame potassium, a flavouring agent, etc..
- a pharmaceutically acceptable excipient or carrier such as an inert diluent, a lubricant such as magnesium stearate, an anti-caking agent such silicon dioxide, a preservative, an antioxidant, a disintegrant, a binder, a thickening agent, a buffer, a sweetener such as acesulfame potassium, a flavouring agent, etc.
- Further dosage forms can be liquid formulations for oral administration including, for example, emulsions, syrups, elixirs, suspensions and solutions.
- the dose of the active ingredients for each patient is determined on the basis of age, body weight, general state of health, gender, diet, condition of the disease treated and/or other factors.
- the quantity of the active ingredients in the composition can range from 75 GalU to 2400 GalU for ⁇ -galactosidase, preferably from 300 GalU to 1200 GalU, and most preferably amounts to 300 GalU in the form of dosage units, and from 2500 to 12500 LactU for ⁇ -galactosidase, preferably from 3500 to 11000 LactU, and most preferably amounts to 4500 LactU in the form of dosage units.
- the dosage unit form is usually administered one or more times a day, as required.
- ⁇ -Galactosidase has proved to prevent the onset of bloating and flatulence symptoms after intake of Non-digestible Oligosaccharides (NDOs) and to reduce the intensity of heartburn and the frequency of regurgitation episodes during repeated administration to patients with gastroesophageal reflux disease.
- NDOs Non-digestible Oligosaccharides
- composition according to the invention in the form of a tablet to be swallowed or chewed contains:
- composition according to the invention in the form of a tablet to be swallowed contains:
Description
- The present invention relates to pharmaceutical or nutritional compositions containing α-galactosidase and β-galactosidase. Said compositions are useful in the prevention and/or treatment of gastroesophageal reflux disease.
- Gastroesophageal reflux disease (GERD), also known as gastro-oesophageal reflux disease (GORD), arises when the stomach contents flow back into the oesophagus.
- It is an extremely common disorder, characterised by heartburn and regurgitation.
- Reflux of the stomach contents into the oesophagus is a physiological phenomenon; when the frequency of the episodes increases, the reflux becomes harmful to the oesophageal mucosa and causes the appearance of symptoms and complications, such as oesophagitis and Barrett's oesophagus.
- As the most harmful constituent of reflux is hydrochloric acid, the treatment is based on suppression of the acid secretion.
- The treatment of GERD greatly improved with the advent of proton pump inhibitors (PPIs), which lead to (endoscopic) healing of oesophagitis in over 90% of cases.
- PPIs therefore represent the first-choice treatment in GERD.
- However, although PPIs reduce the acidity of the gastric juices, the number of reflux episodes remains unchanged, so the oesophageal mucosa is still exposed to the action of the gastric juices.
- H2 antihistamines (anti-H2s) and antacids are also used to treat the symptoms of gastroesophageal reflux disease.
- Despite the availability of various therapeutic approaches, the success rates are much lower if remission and improvement of symptoms are also considered.
- Up to 40% of GERD patients have poorly controlled symptoms, which indicates that there is still a need for new therapeutic agents to treat the disorder.
- Moreover, there is known to be a relationship between diet and reflux. For example, it is known that a meal rich in fats increases the symptoms of reflux and the frequency of reflux episodes by reducing the pressure of the lower oesophageal sphincter. The relationship between other constituents of the diet and reflux is less well known.
- It has been demonstrated that the administration of lactose to volunteers increases acid reflux episodes and markedly influences the function of the lower oesophageal sphincter. The effects of lactose are mediated by the production of short-chain fatty acids, which derive from the metabolism of lactose by the bacterial flora of the colon (Piche et al., 2000; Am J Physiol Gastrointest Liver Physiol 278: G578-84).
- The administration of fructo-oligosaccharides (FOS) also induces effects on the pressure of the lower oesophageal sphincter and the pH of the oesophageal lumen similar to those observed with lactose administration (Piche et al., Gastroenterology 2003; 124: 894-902).
- These data suggest that fermentation in the colon of wholly or partly unabsorbed carbohydrates may be responsible for the onset or aggravation of gastroesophageal reflux disease.
- A preliminary study (9 cases - methodologically elegant and placebo-controlled) has demonstrated that a preparation based on alpha-galactosidase acts as reflux inhibitor (Grossi et al., Digestive and Liver Disease 41S: FISMAD Milan, 28/3-1/4 2009; S49 - Abstract).
- In that study, the administration of alpha-galactosidase for 4 weeks reduced the frequency of Transient Lower Oesophageal Sphincter Relaxations (TLES relaxation), reflux episodes, the percentage of pH < 4 and the severity of the reflux symptoms.
- As the disorder is so widespread, there is still a need to use alternative compositions for the prevention and/or treatment of gastroesophageal reflux disease.
- The present invention relates to pharmaceutical or nutritional compositions containing α-galactosidase and β-galactosidase.
- The invention also relates to the use of said compositions in the prevention and/or treatment of gastroesophageal reflux disease.
- The present invention relates to pharmaceutical or nutritional compositions containing α-galactosidase and β-galactosidase as active ingredients.
- It has now surprisingly been found that pharmaceutical or nutritional compositions containing α-galactosidase and β-galactosidase are useful in the prevention and/or treatment of gastroesophageal reflux disease (GERD). Said compositions have a different action mechanism from those of the medicaments currently used (acid secretion inhibitors) in that they inhibit reflux or at least reduce its frequency.
- The present invention represents a new therapeutic strategy, which is designed in particular for non-responders and patients with a poor response to the current treatments based on proton pump inhibitors.
- The pharmaceutical or nutritional compositions to which the present invention relates can be also added to the existing treatments (as an "add-on therapy"), leading to a significant improvement in the quality of life of many patients with gastroesophageal reflux disease.
- The present invention relates to pharmaceutical or nutritional compositions containing a combination of the active ingredients, mixed with at least one pharmaceutically acceptable excipient or carrier.
- Said compositions are preferably administered orally.
- The pharmaceutical or nutritional compositions for the prevention and/or treatment of gastroesophageal reflux disease containing α-galactosidase and β-galactosidase as active ingredients can be formulated by conventional methods.
- The preferable dosage forms are solid formulations for oral administration, such as powders, granules, tablets, pills and capsules.
- When these compositions are prepared, the active ingredients can be mixed with at least one pharmaceutically acceptable excipient or carrier, such as an inert diluent, a lubricant such as magnesium stearate, an anti-caking agent such silicon dioxide, a preservative, an antioxidant, a disintegrant, a binder, a thickening agent, a buffer, a sweetener such as acesulfame potassium, a flavouring agent, etc..
- Further dosage forms can be liquid formulations for oral administration including, for example, emulsions, syrups, elixirs, suspensions and solutions.
- The dose of the active ingredients for each patient is determined on the basis of age, body weight, general state of health, gender, diet, condition of the disease treated and/or other factors.
- The quantity of the active ingredients in the composition can range from 75 GalU to 2400 GalU for α-galactosidase, preferably from 300 GalU to 1200 GalU, and most preferably amounts to 300 GalU in the form of dosage units, and from 2500 to 12500 LactU for β-galactosidase, preferably from 3500 to 11000 LactU, and most preferably amounts to 4500 LactU in the form of dosage units.
- The dosage unit form is usually administered one or more times a day, as required.
- α-Galactosidase has proved to prevent the onset of bloating and flatulence symptoms after intake of Non-digestible Oligosaccharides (NDOs) and to reduce the intensity of heartburn and the frequency of regurgitation episodes during repeated administration to patients with gastroesophageal reflux disease.
- The combination of α-galactosidase and β-galactosidase has provided an unexpected symptomatic benefit in some patients, who respond unsatisfactory to conventional therapy based on PPI. There is initial evidence that the combination of the two substances boosts the effects by reducing the frequency and duration of reflux to an extent which is markedly high.
- The examples given below further illustrate the invention.
- The composition according to the invention in the form of a tablet to be swallowed or chewed contains:
- 69 mg β-galactosidase (65000 LactU/g)
- 30 mg α-galactosidase (10000 GalU/g)
- 280 mg sorbitol
- 22.78 mg flavouring
- 8 mg crosslinked sodium carboxymethylcellulose
- 8 mg magnesium stearate
- 2 mg silicon dioxide
- 0.22 mg acesulfame potassium
- The composition according to the invention in the form of a tablet to be swallowed contains:
- 69 mg β-galactosidase (65000 LactU/g)
- 30 mg α-galactosidase (10000 GalU/g)
- 280 mg sorbitol
- 8 mg crosslinked sodium carboxymethylcellulose
- 8 mg magnesium stearate
- 2 mg silicon dioxide
- 30 mg ginger (Zingiber officinale) extract
Claims (2)
- Pharmaceutical or nutritional compositions containing α-galactosidase and β-galactosidase, wherein the content of α-galactosidase ranges from 75 and 2400 GaIU and the content of β-galactosidase ranges from 2500 to 12500 LactU, in the form of a dosage unit and at least one pharmaceutically acceptable excipients or carrier.
- Pharmaceutical or nutritional composition according to claim 1 for use in the prevention and /or treatment of gastroesophageal reflux disease.
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MEP-2015-159A ME02285B (en) | 2011-06-24 | 2012-06-21 | Pharmaceutical compositions containing beta- and alpha-galactosidase and their use in the treatment of gastroesophageal reflux disease |
PL12172907T PL2537528T3 (en) | 2011-06-24 | 2012-06-21 | Pharmaceutical compositions containing beta- and alpha-galactosidase and their use in the treatment of gastroesophageal reflux disease |
SI201230335T SI2537528T1 (en) | 2011-06-24 | 2012-06-21 | Pharmaceutical compositions containing beta- and alpha-galactosidase and their use in the treatment of gastroesophageal reflux disease |
HRP20151082TT HRP20151082T1 (en) | 2011-06-24 | 2015-10-13 | Pharmaceutical compositions containing beta- and alpha-galactosidase and their use in the treatment of gastroesophageal reflux disease |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT001154A ITMI20111154A1 (en) | 2011-06-24 | 2011-06-24 | PHARMACEUTICAL OR NUTRITIONAL COMPOSITIONS INCLUDING GALACTOSIDASE AND THEIR USE |
Publications (2)
Publication Number | Publication Date |
---|---|
EP2537528A1 EP2537528A1 (en) | 2012-12-26 |
EP2537528B1 true EP2537528B1 (en) | 2015-09-16 |
Family
ID=44534538
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP12172907.3A Active EP2537528B1 (en) | 2011-06-24 | 2012-06-21 | Pharmaceutical compositions containing beta- and alpha-galactosidase and their use in the treatment of gastroesophageal reflux disease |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP2537528B1 (en) |
DK (1) | DK2537528T3 (en) |
ES (1) | ES2548546T3 (en) |
HR (1) | HRP20151082T1 (en) |
HU (1) | HUE025669T2 (en) |
IT (1) | ITMI20111154A1 (en) |
ME (1) | ME02285B (en) |
PL (1) | PL2537528T3 (en) |
PT (1) | PT2537528E (en) |
RS (1) | RS54325B1 (en) |
SI (1) | SI2537528T1 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9402885B2 (en) * | 2013-07-15 | 2016-08-02 | Alfa Wassermann S.P.A. | Method of treating GERD with alpha and beta galactosidases |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0176971A3 (en) * | 1984-09-29 | 1987-12-02 | Wakamoto Pharmaceutical Co., Ltd. | Gene coding for thermostable beta-galactosidase, bacillus subtilis having the gene, enzyme coded by the gene and a process for the production thereof |
NZ233582A (en) * | 1989-05-16 | 1992-05-26 | Akpharma Inc Formerly Aek Dev | Oral composition comprising alpha-galactosidase |
DE202006012340U1 (en) * | 2006-08-10 | 2007-09-20 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Pharmaceutical composition, in particular for use in food intolerances |
-
2011
- 2011-06-24 IT IT001154A patent/ITMI20111154A1/en unknown
-
2012
- 2012-06-21 PT PT121729073T patent/PT2537528E/en unknown
- 2012-06-21 DK DK12172907.3T patent/DK2537528T3/en active
- 2012-06-21 SI SI201230335T patent/SI2537528T1/en unknown
- 2012-06-21 RS RS20150628A patent/RS54325B1/en unknown
- 2012-06-21 HU HUE12172907A patent/HUE025669T2/en unknown
- 2012-06-21 ME MEP-2015-159A patent/ME02285B/en unknown
- 2012-06-21 EP EP12172907.3A patent/EP2537528B1/en active Active
- 2012-06-21 PL PL12172907T patent/PL2537528T3/en unknown
- 2012-06-21 ES ES12172907.3T patent/ES2548546T3/en active Active
-
2015
- 2015-10-13 HR HRP20151082TT patent/HRP20151082T1/en unknown
Also Published As
Publication number | Publication date |
---|---|
PT2537528E (en) | 2015-11-02 |
DK2537528T3 (en) | 2015-10-26 |
RS54325B1 (en) | 2016-02-29 |
SI2537528T1 (en) | 2015-12-31 |
HRP20151082T1 (en) | 2015-12-04 |
HUE025669T2 (en) | 2016-05-30 |
PL2537528T3 (en) | 2015-12-31 |
ITMI20111154A1 (en) | 2012-12-25 |
EP2537528A1 (en) | 2012-12-26 |
ES2548546T3 (en) | 2015-10-19 |
ME02285B (en) | 2016-02-20 |
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